EP0678023B1 - Verwendung von riluzol zur behandlung von parkinson und den parkinson-syndromen - Google Patents

Verwendung von riluzol zur behandlung von parkinson und den parkinson-syndromen Download PDF

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Publication number
EP0678023B1
EP0678023B1 EP94903935A EP94903935A EP0678023B1 EP 0678023 B1 EP0678023 B1 EP 0678023B1 EP 94903935 A EP94903935 A EP 94903935A EP 94903935 A EP94903935 A EP 94903935A EP 0678023 B1 EP0678023 B1 EP 0678023B1
Authority
EP
European Patent Office
Prior art keywords
riluzole
treatment
parkinson
disease
application
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP94903935A
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English (en)
French (fr)
Other versions
EP0678023A1 (de
Inventor
Alain Boireau
Adam Doble
Pierre Dubedat
Erik Louvel
Mireille Meunier
Jean-Marie Miquet
Jean-Marie Stutzmann
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Aventis Pharma SA
Original Assignee
Rhone Poulenc Rorer SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Rhone Poulenc Rorer SA filed Critical Rhone Poulenc Rorer SA
Publication of EP0678023A1 publication Critical patent/EP0678023A1/de
Application granted granted Critical
Publication of EP0678023B1 publication Critical patent/EP0678023B1/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • the present invention relates to a new therapeutic application of riluzole (6-trifluoromethoxy-2-amino-benzothiazole) or the pharmaceutically acceptable salts of this compound.
  • Riluzole is useful as an anticonvulsant, anxiolytic and hypnotic drug (patent EP 50551), in the treatment of schizophrenia (EP 305276), in the treatment of sleep disorders and depression (EP 305277), in the treatment of cerebrovascular disorders and as an anesthetic (EP 282971).
  • this compound can also be used in the treatment of Parkinson's disease and parkinsonian syndromes.
  • mice The activity of riluzole was therefore demonstrated in mice by measuring the decreases in striatal and cortical dopamine levels induced by MPTP compared to those of control animals.
  • mice 15 mg / kg of MPTP is injected 3 times at 2 hour intervals intraperitoneally into mice (C57BL / 6) weighing 20-25 g.
  • Thirty minutes before the first injection of MPTP then 2 hours and 30 minutes, 5 hours and 30 minutes and 7 hours and 30 minutes after the first injection of MPTP is administered according to the product from 1 to 40 mg / kg of the product to be studied.
  • twice a day according to the product is administered from 1 to 40 mg / kg of the product to be studied.
  • the mice are sacrificed 8 days later MPTP injection.
  • the striatum and the frontal cortex are dissected and stored at -70 ° C until the moment of their analysis. Dopamine levels are measured by high pressure liquid chromatography with electrochemical detection. Statistical analyzes are performed using ANOVA followed by the SCHEFFE test.
  • salts with mineral acids such as hydrochloride, sulphate, nitrate, phosphate or organic salts such as acetate, propionate, succinate, oxalate, benzoate, fumarate, maleate, methanesulfonate, isethionate, theophillin- acetate, salicylate, phenolphthalinate, methylene-bis- ⁇ -oxynaphthoate or substitution derivatives of these derivatives.
  • mineral acids such as hydrochloride, sulphate, nitrate, phosphate or organic salts such as acetate, propionate, succinate, oxalate, benzoate, fumarate, maleate, methanesulfonate, isethionate, theophillin- acetate, salicylate, phenolphthalinate, methylene-bis- ⁇ -oxynaphthoate or substitution derivatives of these derivatives.
  • the medicaments consist of at least riluzole in free form or in the form of an addition salt with a pharmaceutically acceptable acid, in the pure state or in the form of a composition in which it is associated with any other pharmaceutical product. compatible, possibly inert or physiologically active.
  • the medicaments according to the invention can be used orally or parenterally.
  • compositions for oral administration tablets, pills, powders (gelatin capsules, cachets) or granules can be used.
  • the active ingredient according to the invention is mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon.
  • inert diluents such as starch, cellulose, sucrose, lactose or silica
  • These compositions can also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a dye, a coating (dragees) or a varnish.
  • compositions for oral administration there may be used pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin.
  • inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin.
  • These compositions can include substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing products.
  • the sterile compositions for parenteral administration can preferably be aqueous or non-aqueous solutions, suspensions or emulsions.
  • solvent or vehicle water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate or other organic solvents can be used. suitable.
  • These compositions can also contain adjuvants, in particular wetting agents, isotonizers, emulsifiers, dispersants and stabilizers. Sterilization can be done in several ways, for example by aseptic filtration, by incorporating sterilizing agents into the composition, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions which can be dissolved at the time of use in sterile water or any other sterile injectable medium.
  • the doses depend on the desired effect, on the duration of the treatment and on the route of administration used; they are generally between 50 and 400 mg per day orally for an adult with unit doses ranging from 25 to 200 mg of active substance.
  • Tablets containing 50 mg of active product having the following composition are prepared according to the usual technique: - Riluzole 50 mg - Mannitol 64 mg - Microcrystalline cellulose 50 mg - Polyvidone excipient 12 mg - Sodium carboxymethyl starch 16 mg - Talc 4 mg - Magnesium stearate 2 mg - Anhydrous colloidal silica 2 mg - Mixture of methyl hydroxypropyl cellulose, polyethylene glycol 6000, titanium dioxide (72-3,5-24,5) qs 1 film-coated tablet finished at 245 mg
  • capsules containing 50 mg of active product having the following composition are prepared: - Riluzole 50 mg - Cellulose 18 mg - Lactose 55 mg - Colloidal silica 1 mg - Sodium carboxymethyl starch 10 mg - Talc 10 mg - Magnesium stearate 1 mg
  • a solution for injection containing 10 mg of active product having the following composition is prepared: - Riluzole 10 mg - Benzoic acid 80 mg - Benzyl alcohol 0.06 cm3 - Sodium benzoate 80 mg - 95% ethanol 0.4 cm3 - Sodium hydroxide 24 mg - Propylene glycol 1.6 cc - Water qs 4 cm3
  • the invention also relates to the process for the preparation of medicaments useful in the treatment of Parkinson's disease and of parkinsonian syndromes comprising mixing riluzole or the pharmaceutically acceptable salts of this compound with one or more compatible and pharmaceutically acceptable diluents and / or adjuvants .
  • the invention also relates to the application of an effective amount of riluzole or pharmaceutically acceptable salts of this compound. in the preparation of drugs intended for the treatment of Parkinson's disease and parkinsonian syndromes in a mannifer, in particular man.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Psychology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Claims (3)

  1. Verwendung von Riluzol oder den pharmazeutisch annehmbaren Salzen dieser Verbindung zur Herstellung von Arzneimitteln für die Behandlung der Parkinson-Krankheit und von Parkinson-Syndromen,
  2. Verwendung gemäß Anspruch 1, um ein Arzneimittel zu erhalten, das 25 bis 200 mg Riluzol enthält.
  3. Verfahren zur Herstellung eines für die Behandlung der Parkinson-Krankheit und von Parkinson-Syndromen verwendbaren Arzneimittels, dadurch gekennzeichnet, daß man Riluzol oder die pharmazeutisch annehmbaren Salze dieser Verbindung mit einem oder mehreren verträglichen und pharmazeutisch annehmbaren Verdünnungsmitteln und/oder Adjuvantien mischt.
EP94903935A 1993-01-07 1994-01-03 Verwendung von riluzol zur behandlung von parkinson und den parkinson-syndromen Expired - Lifetime EP0678023B1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9300074A FR2700117B1 (fr) 1993-01-07 1993-01-07 Application d'anticonvulsivants dans le traitement de la maladie de Parkinson et des syndromes parkinsoniens.
FR9300074 1993-01-07
PCT/FR1994/000003 WO1994015601A1 (fr) 1993-01-07 1994-01-03 Application du riluzole dans le traitement de la maladie de parkinson et des syndromes parkinsoniens

Publications (2)

Publication Number Publication Date
EP0678023A1 EP0678023A1 (de) 1995-10-25
EP0678023B1 true EP0678023B1 (de) 1996-10-23

Family

ID=9442862

Family Applications (2)

Application Number Title Priority Date Filing Date
EP94903936A Expired - Lifetime EP0678026B1 (de) 1993-01-07 1994-01-03 Verwendung von carbamazepine und oxcarbazepine zur behandlung von parkinson und den parkinson-syndromen
EP94903935A Expired - Lifetime EP0678023B1 (de) 1993-01-07 1994-01-03 Verwendung von riluzol zur behandlung von parkinson und den parkinson-syndromen

Family Applications Before (1)

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EP94903936A Expired - Lifetime EP0678026B1 (de) 1993-01-07 1994-01-03 Verwendung von carbamazepine und oxcarbazepine zur behandlung von parkinson und den parkinson-syndromen

Country Status (23)

Country Link
US (2) US5674885A (de)
EP (2) EP0678026B1 (de)
JP (2) JP3120153B2 (de)
KR (2) KR100298807B1 (de)
AT (2) ATE144420T1 (de)
AU (3) AU5819094A (de)
CA (2) CA2153341A1 (de)
CZ (2) CZ284363B6 (de)
DE (2) DE69400435T2 (de)
DK (2) DK0678023T3 (de)
ES (2) ES2092890T3 (de)
FR (1) FR2700117B1 (de)
GR (2) GR3020975T3 (de)
HU (2) HUT72074A (de)
IL (3) IL108286A0 (de)
MX (2) MX9307885A (de)
NO (2) NO307495B1 (de)
PL (2) PL309596A1 (de)
RU (1) RU2221563C2 (de)
SK (2) SK279645B6 (de)
UA (1) UA29464C2 (de)
WO (3) WO1994015607A1 (de)
ZA (3) ZA9428B (de)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6119094A (en) * 1996-02-29 2000-09-12 Electronic Data Systems Corporation Automated system for identifying alternate low-cost travel arrangements
US6417210B1 (en) * 1998-01-09 2002-07-09 Mor-Research Applications Ltd. Treatment of dyskinesias and Parkinson's disease with riluzole and levodopa
CN1290166A (zh) * 1998-01-09 2001-04-04 Mor－研究应用有限公司 运动障碍的治疗
FR2774592B1 (fr) * 1998-02-06 2000-03-17 Rhone Poulenc Rorer Sa Application du 2-amino-6-trifluoromethoxybenzothiazole pour la prevention ou le traitement des dysfonctionnements du cervelet
FR2777781B1 (fr) 1998-04-24 2004-04-09 Rhone Poulenc Rorer Sa Associations riluzole et l-dopa pour le traitement de la maladie de parkinson
FR2787028B1 (fr) 1998-12-15 2002-10-18 Aventis Pharma Sa Utilisation du riluzole dans le traitement des traumatismes acoustiques
US6506378B1 (en) 1998-12-16 2003-01-14 Arch Development Corporation Vesicular monoamine transporter gene therapy in Parkinson's disease
FR2801793B1 (fr) * 1999-12-01 2003-07-04 Aventis Pharma Sa Association d'une ergoline et de riluzole et son utilisation comme medicament
WO2002064557A2 (en) * 2001-02-12 2002-08-22 Teva Pharmaceutical Industries Ltd. New crystal forms of oxcarbazepine and processes for their preparation
WO2005000294A1 (en) * 2003-06-06 2005-01-06 Pharmacia Corporation Selective inhibitor and an anticonvulsant agent for the treatment of central nervous system disorders
WO2005037276A1 (en) * 2003-10-09 2005-04-28 Aventis Pharma S.A. Use of riluzole for the treatment of essential tremor
CA2471666C (en) * 2004-06-18 2009-10-13 Apotex Pharmachem Inc. An improved process for the preparation of oxcarbazepine and related intermediates
CA2661448A1 (en) 2005-08-25 2007-03-01 Steven Michael Weiss Reducing myocardial damage and the incidence of arrhythmia arising from loss, reduction or interruption in coronary blood flow
US20070178164A1 (en) * 2006-01-31 2007-08-02 Sigal Blau Pharmaceutical formulations of oxcarbazepine and methods for its preparation
US20070248684A1 (en) * 2006-01-31 2007-10-25 Sigal Blau Pharmaceutical formulations of oxcarbazepine and methods for its preparation
GB0603008D0 (en) * 2006-02-14 2006-03-29 Portela & Ca Sa Method
CA2597740C (en) * 2006-04-26 2012-10-16 Supernus Pharmaceuticals, Inc. Modified-release preparations containing oxcarbazepine and derivatives thereof
EP2212344B1 (de) * 2007-09-14 2014-03-26 Formycon AG Verwendung von slit, nephrin, ephrin oder semaphorin zur behandlung von knorpelerkrankungen
EP2389187B1 (de) 2009-01-20 2016-11-16 Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center Sorbin- und benzoesäure und derivate daraus zur verstärkung der wirkung eines neuropharmakons
WO2011017319A1 (en) * 2009-08-03 2011-02-10 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Methods of treating disorders associated with protein polymerization
US8809617B2 (en) * 2009-11-05 2014-08-19 The University of Pittsburgh—Of the Commonwealth System of Higher Education Automated high-content live animal drug screening using C. elegans
US9072772B2 (en) 2009-11-05 2015-07-07 University of Pittsburgh—of the Commonwealth System of Higher Education Methods of treating disorders associated with protein aggregation
WO2014172372A1 (en) 2013-04-15 2014-10-23 Northwestern University Treatment for dopaminergic disorders
ES2936094T3 (es) 2016-06-13 2023-03-14 Syneurx Int Taiwan Corp Cocristales de benzoato de sodio y usos de los mismos
RU2022101542A (ru) 2016-06-13 2022-02-03 Сайньюрекс Интернэшнл (Тайвань) Корп. Сокристаллы бензоата лития и их применения
US11369579B2 (en) 2016-10-24 2022-06-28 Syneurx International (Taiwan) Corp. Polymorphic forms of sodium benzoate and uses thereof
US10336679B2 (en) 2016-10-24 2019-07-02 Syneurx International (Taiwan) Corp. Polymorphic forms of sodium benzoate and uses thereof
US10322114B2 (en) 2017-07-31 2019-06-18 Above And Beyond Nb, Llc Formulation of a riluzole solution with beta-cyclodextrins
US10098861B1 (en) 2017-10-24 2018-10-16 Syneurx International (Taiwan) Corp. Pharmaceutical composition comprising sodium benzoate compound and clozapine, and uses thereof
WO2021055890A1 (en) * 2019-09-20 2021-03-25 Icahn School Of Medicine At Mount Sinai Controlled release formulations of riluzole and their uses

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2948718A (en) * 1960-08-09 New n-heterocyclic compounds
CH500196A (de) * 1969-03-10 1970-12-15 Ciba Geigy Ag Verfahren zur Herstellung von neuen Azepinderivaten
FR2492258A1 (fr) * 1980-10-17 1982-04-23 Pharmindustrie Nouveau medicament a base d'amino-2 trifluoromethoxy-6 benzothiazole
US4431641A (en) * 1980-10-17 1984-02-14 Ciba-Geigy Corporation Pharmaceutical compositions having antiepileptic and antineuralgic action
GB8613183D0 (en) * 1986-05-30 1986-07-02 Wellcome Found Triazine salt
DE4118740A1 (de) * 1991-06-05 1992-12-10 Schering Ag Neue kombinationspraeparate zur behandlung des morbus parkinson
FR2699077B1 (fr) * 1992-12-16 1995-01-13 Rhone Poulenc Rorer Sa Application d'anticonvulsivants dans le traitement de lésions neurologiques liées à des traumatismes.

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
Brain Research, vol. 592, 1992, pages 74-83 *
European Journal of Pharmacology, vol. 235, 1993, pages 297-300 *
J. Neural Transm. (Suppl.), vol. 43, 1994, pages 81-89 *
J. Neural Transm., vol. 3, 1991, pages 203-213 *
Journal of Neurochemistry, vol. 58 (5), 1992, pages 1979-1982 *
Journal of Neurochemistry, vol. 65 (2), 1995, pages 652-659 *
The Journal of Neuroscience, vol 7 (10), 1987, pages 3343-3349 *

Also Published As

Publication number Publication date
FR2700117A1 (fr) 1994-07-08
NO307495B1 (no) 2000-04-17
EP0678023A1 (de) 1995-10-25
PL309594A1 (en) 1995-10-30
CZ176495A3 (en) 1995-12-13
NO952309L (no) 1995-06-12
JPH08505379A (ja) 1996-06-11
HUT72328A (en) 1996-04-29
MX9400287A (es) 1994-07-29
RU2221563C2 (ru) 2004-01-20
NO952310D0 (no) 1995-06-12
ZA9426B (en) 1994-08-11
KR100298807B1 (ko) 2001-11-22
SK86695A3 (en) 1996-05-08
PL309596A1 (en) 1995-10-30
NO952309D0 (no) 1995-06-12
GR3020975T3 (en) 1996-12-31
WO1994015607A1 (fr) 1994-07-21
SK86795A3 (en) 1995-11-08
IL108286A0 (en) 1994-04-12
IL108285A0 (en) 1994-04-12
US5658900A (en) 1997-08-19
KR960700059A (ko) 1996-01-19
CA2153340C (fr) 2002-12-17
DK0678026T3 (da) 1996-09-16
DE69400435T2 (de) 1997-03-06
DE69400799T2 (de) 1997-03-13
WO1994015601A1 (fr) 1994-07-21
ZA9432B (en) 1994-08-11
JPH08505378A (ja) 1996-06-11
GR3021438T3 (en) 1997-01-31
SK279645B6 (sk) 1999-01-11
HUT72074A (en) 1996-03-28
AU677279B2 (en) 1997-04-17
AU5818994A (en) 1994-08-15
HU9502063D0 (en) 1995-09-28
ATE144420T1 (de) 1996-11-15
HU9502065D0 (en) 1995-09-28
DE69400435D1 (de) 1996-10-02
AU5818894A (en) 1994-08-15
JP3120153B2 (ja) 2000-12-25
WO1994015610A1 (fr) 1994-07-21
CZ176595A3 (en) 1995-12-13
EP0678026B1 (de) 1996-08-28
CA2153341A1 (fr) 1994-07-21
ES2091689T3 (es) 1996-11-01
NO952310L (no) 1995-06-12
US5674885A (en) 1997-10-07
CZ284363B6 (cs) 1998-11-11
ZA9428B (en) 1994-08-11
AU5819094A (en) 1994-08-15
EP0678026A1 (de) 1995-10-25
UA29464C2 (uk) 2000-11-15
FR2700117B1 (fr) 1995-02-03
ATE141792T1 (de) 1996-09-15
DE69400799D1 (de) 1996-11-28
KR960700054A (ko) 1996-01-19
IL108284A (en) 1999-03-12
MX9307885A (es) 1994-07-29
SK279758B6 (sk) 1999-03-12
HU217136B (hu) 1999-11-29
CA2153340A1 (fr) 1994-07-21
CZ284928B6 (cs) 1999-04-14
AU684059B2 (en) 1997-12-04
ES2092890T3 (es) 1996-12-01
DK0678023T3 (da) 1996-11-25
IL108284A0 (en) 1994-04-12

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